MitoTEMPOL, a Mitochondrial Targeted Antioxidant, Prevents Sepsis Induced Diaphragm Dysfunction.

MitoTEMPOL, a Mitochondrial Targeted Antioxidant, Prevents Sepsis Induced Diaphragm Dysfunction. Am J Physiol Lung Cell Mol Physiol. 2020 May 27;: Authors: Supinski GS, Wang L, Schroder EA, Callahan LAP Abstract Clinical studies indicate that sepsis induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation, we therefore hypothesized that therapies which target mitochondrial free radical production may prevent sepsis induced diaphragm weakness. The present study determined if MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: (a) sham operated controls, (b) animals with sepsis induced by cecal ligation puncture (CLP), (c) sham controls given MitoTEMPOL (10 mg/kg/d, intraperitoneally), and (d) CLP animals given MitoTEMPOL. At 48 hours after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 hours) on CLP induced diaphragm weakness. The effects of MitoTEMPOL on cytokine mediated alterations on muscle cell superoxide...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research